Serum folic acid levels and erectile dysfunction: A meta-analysis and systematic review

The aim of this study was to assess the relationship between serum folic acid (FA) levels and erectile dysfunction (ED) through a meta-analysis. A research was conducted in MEDLINE via PubMed, Cochrane Library, EMBASE and Web of Science up to 22 November 2020 to identify studies related to FA and ED. Two authors independently screened the literature, evaluated methodological quality and extracted the data. We used RevMan5.3 and STATA 14.0 for meta-analysis. A total of six studies including 1,842 participants were included, and the results showed that the FA levels in the non-ED group were significantly higher than those in the ED group (MD = 3.37, 95% CI 1.49–5.52, p = 0.004). Subgroup analysis indicated that with the increase in ED severity, the difference in FA levels between groups was more obvious (MD: 1.99 vs. 4.63 vs. 5.63). The differences in FA levels between groups seem more significant in the younger group (MD = 4.87, 95% CI 2.58–6.89, p < 0.001) than in the older group (MD = 3.15, 95% CI 2.21–4.08, p < 0.001). In conclusion, FA deficiency is closely related to ED, and the degree of FA deficiency may reflect the severity of ED. In addition, the association seems to be more pronounced in the younger group.     

Chinese herb formulae for treatment of erectile dysfunction: a systematic review of randomised controlled clinical trials

To assess the beneficial and adverse effects of orally therapies of Chinese herb formulae (CHF) for erectile dysfunction (ED), four electronic databases were searched until 23 June 2012. Randomised clinical trials testing CHF or combined with Western medicine therapy (WMT) against placebo, another different CHF and WMT were included. Study selection, data extraction, assessing of bias risk and data analysis were conducted according to the Cochrane handbook. Twenty‐one randomised controlled clinical trials (involving 2253 patients) were included, and the bias risks were not low. Funnel plots of comparing CHF to another CHF on the clinical comprehensive effectiveness were asymmetrical. The compositions of CHF used were greatly complex. The analyses showed that some CHF or combined with WMT had significant effects on cure rate, total clinical effective rates, IIEF‐5 scores, erectile quality scores, erection angles of penis and recovery times of erection compared with the controls. Eight trials reported mild adverse drug reactions, mostly involving gastrointestinal symptoms. It was concluded that some therapies of CHF may be more effective than the controls for treatment of ED. However, because of the generally not low risks of bias, CHF are not recommended for ED. Further research that demonstrates their mechanisms of action and meaningful efficacies must be carried out by rigorously designed, randomised controlled trials.     

The role of N-acetyl-cysteine (NAC) orally daily on the sperm parameters and serum hormones in idiopathic infertile men: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to access the role of N-acetyl-cysteine (NAC) orally daily on the sperm parameters and serum hormones in idiopathic infertile men. Randomised controlled trials (RCTs) were retrieved using PubMed, EMBASE and Cochrane register databases. The references of included studies were also searched. Finally, three articles including 431 infertile men were analysed. The results indicated that the NAC group had a considerable improvement in sperm concentration (mean difference [MD], 3.80; p < .00001), ejaculate volume (MD, 0.69; p = .002), sperm motility (MD, 4.69; p < .0001) and normal morphology (MD, 1.68; p = .0002) compared with the placebo group. However, in terms of serum hormones, the NAC group did not show significant difference in increasing the serum levels of testosterone (MD, 1.35; p = .21), luteinising hormone (MD, 0.82; p = .40), follicle-stimulating hormone (MD, −7.48; p = .29) and prolactin (MD, −0.34; p = .32) compared with the placebo group. In conclusion, NAC orally daily produced a greater improvement in sperm concentration, ejaculate volume, sperm motility and normal morphology for idiopathic infertile men, whereas no significant influence in serum hormones, which required more high-quality RCTs with sufficient sample sizes and statistics to prove.     

A systematic review of reporting quality for anaesthetic interventions in randomised controlled trials

Interventions from randomised controlled trials can only be replicated if they are reported in sufficient detail. The results of trials can only be confidently interpreted if the delivery of the intervention was systematic and the protocol adhered to. We systematically reviewed trials of anaesthetic interventions published in 12 journals from January 2016 to September 2019. We assessed the detail with which interventions were reported, using the Consolidated Standards of Reporting Trials statement for non-pharmacological treatments. We analysed 162 interventions reported by 78 trials in 18,675 participants. Detail sufficiently precise to replicate the intervention was reported for 111 (69%) interventions. Intervention standardisation was reported for 135 (83%) out of the 162 interventions, and protocol adherence was reported for 20 (12%) interventions. Sixty (77%) out of the 78 trials reported the administrative context in which interventions were delivered and 36 (46%) trials detailed the expertise of the practitioners. We conclude that bespoke reporting tools should be developed for anaesthetic interventions and interventions in other areas such as critical care.     

Efficacy of phosphodiesterase type 5 inhibitors in patients with erectile dysfunction after nerve-sparing radical prostatectomy: a systematic review and meta-analysis

BackgroundNerve-sparing radical prostatectomy (NSRP) had to be performed because approximately 94% of patients are diagnosed with localized prostate cancer (PCa). Although NSRP is generally done to improve functional outcomes, erectile dysfunction (ED) is one of the most prevailing complications after radical prostatectomy (RP). Phosphodiesterase type 5 inhibitors (PDE5-Is) are the most well-known treatment agent for postoperative ED. This study aimed to assess the efficacy of PDE5-Is in patients with ED after NSRP.MethodsIn this systematic literature review, randomized controlled trials on the efficacy and safety of PDE5-Is in patients who underwent NSRP were searched in MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the OVID platform. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Review Methods. The quality of the evidence of the outcome data was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.ResultsA total of 14 trials involving 2,822 patients were included. Significant improvements in the International Index of Erectile Function—Erectile Function (IIEF) domain score [mean difference (MD) =4.93; 95% confidence interval (CI): 4.14–5.71; P<0.00001] and erectile function recovery events [odds ratio (OR) =2.06; 95% CI: 1.45–2.94; P<0.0001] were observed after PDE5-I treatment. A higher positive response to Sexual Encounter Profile (SEP) question 2 (OR =2.27; 95% CI: 1.80–2.86; P<0.00001) and question 3 (OR =2.78; 95% CI: 1.97–3.91; P<0.00001) was also found after PDE5-I treatment. However, the incidence of treatment-emergent adverse events (TEAEs) was higher after PDE5-I treatment than after placebo treatment (OR =2.91; 95% CI: 1.84–4.61). Furthermore, the incidence of headache (OR =3.38; 95% CI: 2.40–4.75) and flushing (OR =9.44; 95% CI: 4.30–20.70) was also significantly higher after PDE5-I treatment (P<0.00001). In terms of the quality of the evidence of the outcome data, inconsistency problems were detected in all outcomes and imprecision problems in most outcomes.DiscussionPDE5-I treatment was more effective to placebo treatment in patients with ED after NSRP. No clinically serious complications were found in spite of the incidence of TEAEs being higher after PDE5-I treatment.     

A meta-regression evaluating the effectiveness and prognostic factors of oral phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction

The effectiveness of phosphodiesterase type 5 inhibitors (PDE5-Is) for erectile dysfunction (ED) varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-Is with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaboration''s tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-Is were grouped together, Caucasian ethnicity was associated with 15.636% (95% confidence interval [CI]: 0.858% to 32.579%) increase in risk ratio (RR) for Global Assessment Questionnaire question-1 (GAQ-1), and 1.473 (95% CI: 0.406 to 2.338) score increase in mean difference (MD) for posttreatment International Index of Erectile Function-Erectile Function domain score (IIEF-EF), compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with −5.635% (95% CI: −9.120% to −2.017%) reduction in RR for GAQ-1, and −0.229 (95% CI: −0.425 to −0.042) score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-Is are more effective in Caucasians than Asians, and in patients with more severe ED.     

Duration of erectile dysfunction and its relationship to treatment seeking and satisfaction with treatment using PDE5 inhibitors

Objectives:   This cross-sectional study was designed to evaluate whether the duration of erectile dysfunction (ED) influenced treatment seeking and satisfaction with treatment using PDE5 inhibitors.
Methods:   Participants were 409 men with ED who were primarily recruited over the internet via men's health web sites. Participants completed a questionnaire to assess the duration and perceived severity of ED, information and help-seeking behaviors for ED, and treatment usage and satisfaction with PDE5 inhibitor medication.
Results:   The results demonstrated that men with ED of longer duration were more likely to have discussed their ED with their partner and doctor and to have sought information and treatment for their ED problem. No differences were found in reported satisfaction with ED medication usage or expected future medication use across the varying levels of ED duration, once variance attributable to age was accounted for.
Conclusions:   These results suggest that men are more likely to accept that they have ED and seek treatment for their ED with increasing duration of the condition, although these men are not more satisfied with PDE5 inhibitors as a treatment option.     

甲磺酸酚妥拉明片治疗男性勃起功能障碍Ⅱ期临床报告

目的评价甲磺酸酚妥拉明片治疗男性勃起功能障碍的有效性及安全性和耐受性。方法220例受试者(试验组112例、对照组108例),采用多中心、随机双盲、安慰剂平行对照、剂量视情增减的设计方案,在2周筛选期后进入4周的治疗期,在筛选期及研究结束时填写国际勃起功能问卷(IIEF)。研究者根据受试者记事表、IIEF和总评题对受试者进行疗效评价。结果主要疗效指标临床总有效率甲磺酸酚妥拉明组(A组)50．94%,安慰剂组(B组)16．82%：总评题：A组有57．55%的受试者认为研究药物改善了其勃起功能,B组22．43%。受试者记事表显示：A组受试者的性生活成功率为49．46%,B组17．88%。,不良反应发生率A组26．17%,B组7．62%,表现为轻度和短暂的鼻塞、面部潮红、心率快、口干、胸闷、胃不适、瘙痒、头痛、头晕、低血压。仅3名受试者因不良事件而终止研究。结论甲磺酸酚妥明片为一种安全、有效的治疗ED的药物。     

Efficacy and safety of phosphodiesterase type 5 inhibitors on primary premature ejaculation in men receiving selective serotonin reuptake inhibitors therapy: a systematic review and meta‐analysis

We performed a systematic review and meta‐analysis to assess whether selective serotonin reuptake inhibitors (SSRIs) and phosphodiesterase type 5 inhibitors ( PDE5‐Is ) may have an additive therapeutic effect. A literature review was performed to identify all published randomised controlled trials (RCT) that used SSRIs combined with PDE5‐Is therapy for the treatment of primary PE. The search included the following databases: EMBASE, MEDLINE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Five publications involving a total of 419 patients were used in the analysis, including 5 RCTs that compared PDE5‐Is plus SSRIs with SSRIs treating primary PE. Primary efficacy endpoints: IELT (the standardised mean difference (SMD) = 1.07, 95% confidence interval (CI) = 1.00 to 1.14, P < 0.00001) indicated that utilisation of PDE5‐Is and SSRIs was more effective than the SSRIs alone for a long time in patients with primary PE. Safety assessments included headache (odds ratio (OR) = 3.16, 95% CI = 1.63 to 6.11, P = 0.0006), and flushing indicated that PDE5‐Is plus SSRIs were well tolerated. This meta‐analysis indicates that PDE5‐Is combined with SSRIs seem to provide significantly better ejaculatory latency time as compared with SSRIs alone in patients with primary PE.     

Comparison of the clinical efficacy of daily use of L-arginine,tadalafil and combined L-arginine with tadalafil in the treatment of elderly patients with erectile dysfunction

This study aimed to evaluate the efficacy of the daily oral administrations of L-arginine, tadalafil and combined L-arginine with tadalafil in treatments of elderly patients with erectile dysfunction (ED). It was designed as a single-blind placebo-controlled clinical trial. It was conducted on 120 male patients aged ≥60 years old with ED. Patients were randomised classified into four groups (n = 30 each). Oral daily use of L-arginine (5 g), tadalafil (5 mg), combined L-arginine (5 g) with tadalafil (5 mg) and placebo were taken for 6 weeks in each group of patients respectively. Patients were assessed before and after treatments using the Sexual Health Inventory for Men (SHIM) questionnaire and total serum testosterone. The means of Q1–5, total scores of SHIM and total testosterone, in L-arginine, tadalafil and combined L-arginine with tadalafil groups were significantly higher after treatments (p = .001). Combined L-arginine with tadalafil group had the highest SHIM scores and levels of total testosterone. This clinical trial deduced that the combined daily use of L-arginine with tadalafil therapy for elderly male patients with ED could significantly increase the SHIM scores and levels of total testosterone in comparison to L-arginine, or tadalafil alone.     

Efficacy and safety of avanafil for treating erectile dysfunction: results of a multicentre,randomized, double‐blind,placebo‐controlled trial

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Avanafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for treating erectile dysfunction (ED). Preclinical and clinical phase I studies showed that avanafil had enhanced selectivity, faster onset of action and a favourable side‐effect profile relative to currently available PDE5 inhibitors. As the result of phase III clinical trial for the efficacy and safety of avanafil treatment (100 and 200 mg), taken as needed over a period of 12 weeks, in Korean patients with ED, avanafil is an effective and well‐tolerated therapy for ED of broad‐spectrum aetiology and severity.

OBJECTIVE

• ? To evaluate the efficacy and safety of avanafil, a new potent selective phosphodiesterase type 5 (PDE5) inhibitor, in patients with erectile dysfunction (ED).

PATIENTS AND METHODS

• ? The present study was a multicentre, randomized, double‐blind, placebo‐controlled, fix‐dosed phase three clinical trial involving 200 patients with ED.
• ? The subjects were treated with placebo or avanafil (100 or 200 mg) for 12 weeks and were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Questionnaire (GAQ).
• ? The primary outcome variable was the change from baseline for IIEF erectile function domain (EFD) score.
• ? The secondary outcome variables were SEP Q2 and Q3, the shift to normal rate (EFD ≥ 26), and response to the GAQ.

RESULTS

• ? Compared with placebo, patients who took 100 or 200 mg of avanafil had significantly improved IIEF‐EFD score.
• ? There were similar results when comparing Q2 and Q3 in the SEP diary and the GAQ.
• ? Flushing was the most common treatment‐related adverse event.
• ? Most adverse events were transient and mild or moderate in severity.

CONCLUSION

• ? Avanafil is an effective and well‐tolerated therapy for ED of broad‐spectrum aetiology and severity.

     

Vardenafil is effective and well-tolerated for treating erectile dysfunction in a broad population of men, irrespective of age

OBJECTIVES

To assess the efficacy and safety of vardenafil in the treatment of erectile dysfunction (ED) in men of different age groups.

PATIENTS AND METHODS

In a retrospective pooled subgroup analysis of randomized, double‐blind, placebo‐controlled studies, men from the general population with ED received either placebo or vardenafil 5, 10 or 20 mg over 12 weeks. Efficacy variables included the erectile function (EF) domain score from The International Index of Erectile Function, diary response rates to questions on vaginal penetration and maintenance of erection, and positive responses to the Global Assessment Question (GAQ) ‘Has the treatment you have been taking over the past 4 weeks improved your erections?’. The 1385 men were grouped by age (<45, 45–64 and ≥65 years).

RESULTS

At 12 weeks the EF domain scores approached 20 with vardenafil and 14 with placebo in men aged ≥ 65 years (P < 0.03 vardenafil 5 mg vs placebo, P < 0.001 vardenafil 10 and 20 mg vs placebo). The corresponding scores were 22 and 14 in men aged 45–64 years and up to 24 and 16 in those aged <45 years (P < 0.03 vardenafil 5 mg vs placebo, P < 0.001 vardenafil 10 and 20 mg vs placebo). Vardenafil generated positive GAQ responses in ≈ 71%, 76% and 85% of men aged <45, 45–64 and ≥ 65 years (P ≤ 0.001 vardenafil vs placebo). The corresponding placebo rates were 23%, 25% and 34%. The most common treatment‐emergent adverse events were headache, rhinitis, flushing and dyspepsia, which were mild to moderate, transient and unrelated to age.

CONCLUSION

Vardenafil is an effective and generally well‐tolerated treatment for ED, irrespective of age.

     

The fragility of statistically significant findings in randomised controlled anaesthesiology trials: systematic review of the medical literature

The fragility index (FI), the number of events the statistical significance a result depends on, and the number of patients lost to follow-up are important parameters for interpreting randomised clinical trial results. We evaluated these two parameters in randomised controlled trials in anaesthesiology. For this, we performed a systematic search of the medical literature, seeking articles reporting on anaesthesiology trials with a statistically significant difference in the primary outcome and published in the top five general medicine journals, or the top 15 anaesthesiology journals. We restricted the analysis to trials reporting clinically important primary outcome measures. The search identified 139 articles, 35 published in general medicine journals and 104 in anaesthesiology journals. The median (inter-quartile range) sample size was 150 (70–300) patients. The FI was 4 (2–17) and 3 (2–7), and the number of patients lost to follow-up was 0 (0–18) and 0 (0–6) patients in trials published in general medicine and anaesthesiology journals, respectively. The number of patients lost to follow-up exceeded the FI in 41 and 27% in trials in general medicine journals and anaesthesiology journals, respectively. The FI positively correlated with sample size and number of primary outcome events, and negatively correlated with the reported P-values. The results of this systematic review suggest that statistically significant differences in randomised controlled anaesthesiology trials are regularly fragile, implying that the primary outcome status of patients lost to follow-up could possibly have changed the reported effect.     

手术干预与传统方法治疗多发性肋骨骨折随机对照研究的系统评价与Meta分析

目的对手术和传统方法治疗多发性肋骨骨折进行系统评价,对比其疗效。方法计算机检索中国期刊全文数据库(CNKI)、万方数据库(Wanfang)、维普期刊数据库(VIP)、PubMed、OVID、EMbase、The Cochrane Library、Thieme及Springer Link数据库。收集有关手术和传统方法治疗多发性肋骨骨折的随机对照研究(RCT),检索时限为各数据库建库至2019年7月。对文献进行筛选、质量评价及数据提取。Meta分析采用RevMan 5.3软件。结果共纳入文献12篇,患者1039例。其中手术组512例,传统组527例。Meta分析显示:两组在肺部感染发生率[RR=0.41,99%CI(0.29,0.58),P<0.00001]、肺不张发生率[RR=0.24,99%CI(0.06,0.94),P=0.007]、呼吸机支持时间[SMD=-2.64,99%CI(-4.38,-0.91),P<0.0001]、住ICU时间[SMD=-1.33,99%CI(-2.26,-0.40),P=0.0002]、总体住院时间[SMD=-2.25,99%CI(-3.30,-1.19),P<0.00001]、胸壁畸形发生率[RR=0.08,99%CI(0.04,0.17),P<0.00001]等方面差异有统计学意义。在住院死亡率[RR=0.75,99%CI(0.23,2.46),P=0.53]、气管切开率[RR=0.69,99%CI(0.39,1.21),P=0.09]、呼吸机支持率[RR=0.65,99%CI(0.41,1.05),P=0.02]、胸腔引流时间[SMD=-2.58,99%CI(-6.41,1.25),P=0.08]等方面差异无统计学意义。结论手术治疗多发性肋骨骨折能够减少肺部并发症、缩短住院时间、降低胸壁畸形发生率,有利于患者快速康复和改善生活质量。     

Efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors in treating erectile dysfunction after bilateral nerve‐sparing radical prostatectomy

We carried out a systematic review and meta‐analysis to assess the efficacy and safety of phosphodiesterase type 5 (PDE5) inhibitors for treating erectile dysfunction (ED) after bilateral nerve‐sparing radical prostatectomy (BNSRP). A literature review was performed to identify all published randomised double‐blind, placebo‐controlled trials of PDE5 inhibitors for the treatment of ED after BNSRP. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Six publications involving a total of 1678 patients were used in the analysis, including six RCTs that compared PDE5 inhibitors (tadalafil, sildenafil, avanafil and vardenafil) with placebo. Co‐primary efficacy end points: International Index of Erectile Function‐Erectile Function (IIEF‐EF) domain score [the standardised mean difference (SMD) = 4.04, 95% confidence interval (CI) = 2.87–5.22, P < 0.00001]; successful vaginal penetration (SEP2) [the odds ratio (OR) = 14.87, 95%CI = 4.57–48.37, P < 0.00001]; and successful intercourse (SEP3) (OR = 47, 95%CI = 3–13.98, P < 0.00001) indicated that PDE5 inhibitors was more effective than the placebo. Specific adverse events with PDE5 inhibitors included headache (12.08%), dyspepsia (6.76%) and flushing (6.52%), which were significantly less likely to occur with placebo. This meta‐analysis indicates that PDE5 inhibitors to be an effective and well‐tolerated treatment for ED after BNSRP.